TRIM52 up-regulation in hepatocellular carcinoma cells promotes proliferation, migration and invasion through the ubiquitination of PPM1A

Autor: Yong-Sheng Yu, Guoqing Zang, Jie Chen, Cui-Cui Xu, Xiaohua Chen, Yi Zhang, Jie-Ling Wang, Shanshan Wu, Ran Tao, Zhenghao Tang
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Cancer Research
Hepatocellular carcinoma
Tripartite Motif Proteins
Mice
0302 clinical medicine
Nude mouse
Cell Movement
Neoplasm Metastasis
TRIM52
biology
medicine.diagnostic_test
Chemistry
Liver Neoplasms
Cell migration
Middle Aged
Cell cycle
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunohistochemistry
Tumor Burden
PPM1A
Gene Expression Regulation
Neoplastic
Protein Phosphatase 2C
Oncology
030220 oncology & carcinogenesis
Heterografts
Female
Adult
Carcinoma
Hepatocellular
lcsh:RC254-282
Flow cytometry
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
medicine
Animals
Humans
Aged
Cell Proliferation
Neoplasm Staging
Cell growth
Research
Ubiquitination
biology.organism_classification
Disease Models
Animal
030104 developmental biology
Apoptosis
Cell culture
Cancer research
Biomarkers
Zdroj: Journal of Experimental & Clinical Cancer Research, Vol 37, Iss 1, Pp 1-13 (2018)
Journal of Experimental & Clinical Cancer Research : CR
ISSN: 1756-9966
DOI: 10.1186/s13046-018-0780-9
Popis: Background Many tripartite motif (TRIM) family proteins have been reported to be of great importance in the initiation and progression in hepatocellular carcinoma (HCC). However, the biological role and regulatory mechanism of tripartite motif containing 52 (TRIM52) in HCC development and progression are poorly defined. Methods Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) or Western blot analysis was used to detect TRIM52, p21, matrix metalloproteinase 2 (MMP2), protein phosphatase, Mg2+/Mn2+ dependent 1A (PPM1A), p-Smad2/3 and Smad2/3 levels in HCC tissues and cell lines. HCC cell proliferation and cell cycle were measured by Cell Counting Kit-8 (CCK-8) and flow cytometry analysis, respectively. HCC cell migration and invasion were measured by Transwell assay. Tumor growth of HCC cells in vivo was measured using the nude mouse xenograft model. The correlation between TRIM52 and PPM1A was measured by co-immunoprecipitation (Co-IP) and ubiquitination analysis in vitro. Results TRIM52 was significantly up-regulated in the HCC tissues in comparison with the adjacent non-tumor hepatic tissues. TRIM52 was also up-regulated in HCC cell lines (MHCC-97H and MHCC-97L cells) compared with normal human liver cell line LO2. TRIM52 down-regulation by RNA interfering in MHCC-97H cells enhanced inhibition of cell proliferation, migration and invasion. TRIM52 down-regulation also induced MHCC-97H cells arrest in G0-G1 phase cell cycle and inhibited MHCC-97H cell growth in the nude mice. However, TRIM52 up-regulation in MHCC-97L cells promoted cell proliferation, migration and invasion. Furthermore, TRIM52 down-regulation significantly increased p21 and PPM1A expression, but inhibited MMP2 expression and induced Smad2/3 dephosphorylation in MHCC-97H cells, which were reversed by TRIM52 up-regulation in MHCC-97L cells. TRIM52 was found interacted with PPM1A and TRIM52 down-regulation inhibited the ubiquitination of PPM1A. Importantly, PPM1A up-regulation in MHCC-97L cells significantly suppressed TRIM52-mediated enhancement on cell proliferation, invasion and migration. Conclusions Our findings suggest that TRIM52 up-regulation promotes proliferation, migration and invasion of HCC cells through the ubiquitination of PPM1A.
Databáze: OpenAIRE
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